ИСТИНА

Nitric oxide (NO) is an important signaling molecule involved in modulating diverse physiological processes such as vasodilatation, immune response, inflammation, and neurotransmission. It has also been implicated in many disorders, including cardiovascular, neurodegenerative, autoimmune diseases, and cancer. Biological effects and possibilities of use of NO-donor molecules, are extensively studied. The major classes of synthetic NO-donor compounds comprise organic nitrates; metal-NO complexes, S-nitrosothiols, sydnonimines, diazeniumdiolates and NO-drug hybrids. Metal containing nitrosyl iron-sulfur complexes (NISCs) are of special interest because of their structural similarity to one of the main NO storage forms in organism. Earlier, numerous NISCs were synthesized and studied. Many of them proved to suppress growth of tumor cell cultures. Some NISCs were shown to have specific toxicity to cancer cells compared to normal cells. One of the mechanisms of biological effects of NO includes S-nitrosylation of proteins. This modification affects cysteines, thus preventing formation of disulfur bonds and modulating functional state of proteins. NF-κB is a transcription factor with wide range of functions. Originally, it was described as a regulator of immune cells; at present its important roles in regulation of the cell division and death are established. NISCs were found to affect functions of NF-κB in cancer cells. It was demonstrated that NISCs can cause S-nitrosylation of NF-κB. NISCs disturb nuclear translocation of NF-κB which in turn leads to inhibition of expression of genes related to cell survival and proliferation. Results of research of NISCs’ impact on state and functions NF-κB in cancer cells are presented, and possible mechanisms underlying the cytotoxic effects of NO-donor NISCs, as well as possibility of their use for chemotherapy are discussed.